The effect of montelukast on atherogenesis in apoE/LDLR-double knockout mice

We have shown that inhibitors of five lipoxygenase activating protein (FLAP)--MK-886 and BAYx1005 inhibit atherosclerosis in apolipoprotein E/LDL receptor-double knockout mice. We, therefore, investigated whether cysteinyl leukotrienes receptor inhibitor--montelukast, given at a dose of 0.125 microg per 100 mg of body weight per day during 16 weeks, could also attenuate atherogenesis. In apoE/LDLR-DKO mouse model montelukast significantly decreased atherogenesis, measured both by "en face" method (25.5+/-2.% vs. 17.23 +/- 1.8%) and "cross-section" method (455,494 +/- 26,477 microm(2) vs. 299,201 +/- 20,373 microm(2)). The results were, however, less pronounced, comparing to FLAP inhibitors. This is the first report showing the effect of montelukast on atherogenesis in gene-targeted mice.